Ladenius A R, Nijkamp F P
Department of Pharmacology, Faculty of Pharmacy, Utrecht University, Netherlands.
Eur J Pharmacol. 1993 Apr 22;235(1):127-31. doi: 10.1016/0014-2999(93)90831-2.
The role of substance P-containing sensory nerves in the development of tracheal hyperreactivity to histamine and arecoline was investigated in an allergic model of asthma. Male Hartley-strain guinea pigs were sensitized to ovalbumin (20 mg/kg i.p.) and 14 days later exposed to either saline or ovalbumin (2%) aerosols for 8 consecutive days. One day after the last aerosol exposure the animals were killed and the tracheas were removed. Isotonic muscle shortening in response to increasing doses of histamine and arecoline was measured. Capsaicin (50 mg/kg s.c.) or vehicle pretreatment was performed 7 days prior to sensitization. Tracheas from vehicle-pretreated sensitized and ovalbumin-aerosol exposed animals had increased reactivity to both histamine and arecoline compared to saline-aerosol exposed animals. Capsaicin pretreatment did not alter tracheal reactivity in the saline-aerosol exposed group. Capsaicin pretreatment prevented the increase in tracheal reactivity caused by both agonists in sensitized and ovalbumin-aerosol exposed guinea pigs. These results suggest that capsaicin-sensitive sensory nerves are important for the development of increased tracheal reactivity in an allergic model of asthma.
在哮喘的过敏模型中,研究了含P物质的感觉神经在气管对组胺和槟榔碱高反应性发展中的作用。雄性Hartley品系豚鼠用卵清蛋白(20mg/kg腹腔注射)致敏,14天后连续8天暴露于生理盐水或卵清蛋白(2%)气雾剂中。最后一次气雾剂暴露后一天,处死动物并取出气管。测量对递增剂量组胺和槟榔碱的等张肌肉收缩。在致敏前7天进行辣椒素(50mg/kg皮下注射)或赋形剂预处理。与暴露于生理盐水气雾剂的动物相比,经赋形剂预处理的致敏且暴露于卵清蛋白气雾剂的动物的气管对组胺和槟榔碱的反应性增加。辣椒素预处理未改变暴露于生理盐水气雾剂组的气管反应性。辣椒素预处理可防止致敏且暴露于卵清蛋白气雾剂的豚鼠中两种激动剂引起的气管反应性增加。这些结果表明,对辣椒素敏感的感觉神经在哮喘过敏模型中气管反应性增加的发展中起重要作用。